This invention relates to the use of a nutritional composition such as an infant formula or a baby food, comprising an n-6 long chain polyunsaturated fatty acid to reduce the risk of the infant developing obesity and insulin resistance later in life.
Mother's milk is recommended for all infants. However, in some cases breast feeding is inadequate or unsuccessful or inadvisable for medical reasons or the mother chooses not to breast feed either at all or for a period of more than a few weeks. Infant formulas have been developed for these situations. Similarly, the infant's nutritional needs remain specific until early childhood. There are situations where the nutritional needs cannot be adequately covered by family foods. Therefore, nutritionally-balanced baby foods designed according to the baby's particular needs are the most appropriate complementary source of nutrition during infancy and early childhood.
The prevalence of obesity and overweight in adults, children and adolescents has increased rapidly over the past 30 years in the United States and globally and continues to rise. Childhood overweight and obesity currently affects 18 million children under age 5 worldwide. Almost 30% of US children and adolescents and between 10 and 30% of European children are overweight or obese.
Increasingly it is believed that the first 6 months of life represent one of the most important postnatal periods for human fat mass development and consequently may be a critical window for programming excess of adiposity later in life. Moreover, human epidemiological data and animal studies evidence that elevated body weight at birth or during infancy are associated with a risk for development of diseases such as insulin resistance syndrome (also called metabolic syndrome), Type 2 diabetes and cardiovascular problems later in life.
Massiera et al. investigated the influence of the long chain, polyunsaturated fatty acid arachidonic acid C20:4, n-6 (ARA) on the differentiation of clonal preadipocytes. They found that, compared to a combination of specific agonists to both peroxisome proliferator-activated receptors 8 and γ or to saturated, mono-unsaturated and n-3 polyunsaturated fatty acids, ARA substantially promoted the differentiation of clonal preadipocytes. They further discovered that this effect was blocked by cyclooxygenase inhibitors and mimicked by carbacyclin suggesting a role for the prostacyclin receptor and activation of the cyclic AMP-dependent pathways that regulate the expression of CCAAT enhancer binding proteins β and δ implicated in adipogenesis. In a study in which different groups of lactating mice were fed either a diet rich in linoleic acid (a precursor of ARA) or an isocaloric diet containing a mixture of linoleic acid and α-linolenic acid, they found that body weight from weaning onwards, fat mass, epididymal fat pad weight and adipocyte size at 8 weeks of age were higher with the linoleic acid-enriched diet. When the same experiment was carried out using prostacyclin receptor-deficient mice, no difference was observed between the groups indicating that the prostacyclin signaling contributes to adipose tissue development. The authors comment that these results may be significant in view of the relatively high content of linoleic acid of infant formula, linoleic acid being a precursor of ARA.
In WO2008/054192, it is claimed that the whole adipose tissue mass of infants is not a good predictor to determine the risks of diseases later in life and that it is rather the accumulation of visceral fat mass in early infancy should be considered. It has been demonstrated that visceral adipocyte count is primarily determined during infancy and it follows that it would be useful to be able to control adipogenesis during this period. Among the possible solutions proposed in WO2008/054192, it is suggested that administration of the n-3 long chain polyunsaturated fatty acids docosahexaenoic acid, stearidonic acid, docosapentaenoic acid and/or eicosapentaenoic acid may reduce accumulation of visceral fat mass whilst maintaining normal growth and development. It is, however, recommended not to include ARA on the basis that ARA counteracts the effect of the n-3 long chain polyunsaturated fatty acids.